NCT04194944 · CITED IN SOURCE DOCUMENTS

A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2025-10-21

The reason for this study is to see if the study drug selpercatinib compared to a standard treatment is effective and safe in participants with rearranged during transfection (RET) fusion-positive non-squamous non-small cell lung cancer (NSCLC) that has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) (With Pembrolizumab)

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outcome · POSTED

PFS by BICR (With or Without Pembrolizumab)

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outcome · POSTED

Percentage of Participant With Disease Control Rate (DCR) by BICR (With Pembrolizumab)

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outcome · POSTED

Percentage of Participant With DCR by BICR (With or Without Pembrolizumab)

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outcome · POSTED

PFS2 (With Pembrolizumab)

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outcome · POSTED

PFS2 (With or Without Pembrolizumab)

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outcome · POSTED

Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR (With Pembrolizumab)

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outcome · POSTED

ORR: Percentage of Participants With CR or PR by BICR (With or Without Pembrolizumab)

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outcome · POSTED

Duration of Response (DoR) by BICR (With Pembrolizumab)

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outcome · POSTED

DOR by BICR (With or Without Pembrolizumab)

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outcome · POSTED

Overall Survival (OS) (With Pembrolizumab)

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outcome · POSTED

OS (With or Without Pembrolizumab)

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outcome · POSTED

Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 by BICR (With Pembrolizumab)

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outcome · POSTED

Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per RECIST 1.1 by BICR (With or Without Pembrolizumab)

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outcome · POSTED

Median Intracranial DOR Per RECIST 1.1 by BICR (With Pembrolizumab)

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outcome · POSTED

Median Intracranial DOR Per RECIST 1.1 by BICR (With or Without Pembrolizumab)

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outcome · POSTED

Time to Deterioration of Pulmonary Symptoms (With Pembrolizumab)

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outcome · POSTED

Time to Deterioration of Pulmonary Symptoms (With or Without Pembrolizumab)

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outcome · NOT POSTED

The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants With RET-Positive Specimens as Called by the Central Lab, Which is Also RET-Positive as Called by a Local Lab (Positive Percent Agreement)

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outcome · POSTED

Median Time to CNS Progression Per RECIST 1.1 by BICR (With Pembrolizumab)

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outcome · POSTED

Median Time to CNS Progression Per RECIST 1.1 by BICR (With or Without Pembrolizumab)

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outcome · NOT POSTED

Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) by BICR (With Pembrolizumab)

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outcome · NOT POSTED

Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per RANO-BM by BICR (With or Without Pembrolizumab)

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outcome · NOT POSTED

Intracranial DOR Per RANO-BM by BICR (With Pembrolizumab)

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outcome · NOT POSTED

Intracranial DOR Per RANO-BM by BICR (With or Without Pembrolizumab)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Histologically or cytologically confirmed, Stage IIIB-IIIC or Stage IV non-squamous NSCLC that is not suitable for radical surgery or radiation therapy. * A RET gene fusion in tumor and/or blood from a qualified laboratory. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Adequate hematologic, hepatic and renal function. * Willingness of men and women of reproductive potential to observe conventional and highly effective birth control for the duration of treatment and for 6 months after. * Ability to swallow capsules. Exclusion Criteria: * Additional validated oncogenic drivers in NSCLC if known. * Prior systemic therapy for metastatic disease. Treatment (chemotherapy, immunotherapy, or biological therapy) in the adjuvant/neoadjuvant setting is permitted if it was completed at least 6 months prior to randomization. * Major surgery within 3 weeks prior to planned start of selpercatinib. * Radiotherapy for palliation within 1 week of the first dose of study treatment or any radiotherapy within 6 months prior to the first dose of study treatment if more than 30 Gy to the lung. * Symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or untreated spinal cord compression. * Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of selpercatinib or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 470 milliseconds. * Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment. * Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug. * Pregnancy or lactation. * Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or other in situ cancers or a malignancy diagnosed ≥2 years previously and not currently active. * Uncontrolled, disease related pericardial effusion or pleural effusion. * Requiring chronic treatment with steroids. Exclusion Criteria for Participants Receiving Pembrolizumab: * History of interstitial lung disease or interstitial pneumonitis. * Active autoimmune disease or any illness or treatment that could compromise the immune system.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
160 milligram (mg) Selpercatinib administered orally twice daily (BID) continuously in 21-day cycles.
intervention Names
Drug: Selpercatinib
label
Selpercatinib - Treatment A (TRT A)
type
EXPERIMENTAL
description
Pemetrexed 500 milligrams per meter squared (mg/m2) administered intravenously (IV) on Day 1, every 3 weeks (Q3W), plus investigator's choice of carboplatin area under the concentration versus time curve 5 (AUC 5 \[maximum dose of 750 mg\] IV), or cisplatin (75 mg/m2 cisplatin IV) on Day 1 Q3W for 4 cycles, plus investigator's choice with or without 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
intervention Names
Drug: Carboplatin
Drug: Cisplatin
Drug: Pemetrexed
Drug: Pembrolizumab
label
Pemetrexed and Platinum with or without Pembrolizumab - (TRT B)
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Selpercatinib - Treatment A (TRT A)
description
Administered orally
name
Selpercatinib
other Names
LY3527723
LOXO-292
type
DRUG
arm Group Labels
Pemetrexed and Platinum with or without Pembrolizumab - (TRT B)
description
Administered IV
name
Carboplatin
type
DRUG
arm Group Labels
Pemetrexed and Platinum with or without Pembrolizumab - (TRT B)
description
Administered IV
name
Cisplatin
type
DRUG
arm Group Labels
Pemetrexed and Platinum with or without Pembrolizumab - (TRT B)
description
Administered IV
name
Pemetrexed
type
DRUG
arm Group Labels
Pemetrexed and Platinum with or without Pembrolizumab - (TRT B)
description
Administered IV
name
Pembrolizumab
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 261
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.
measure
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) (With Pembrolizumab)
time Frame
Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
description
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.
measure
PFS by BICR (With or Without Pembrolizumab)
time Frame
Baseline to Progressive Disease or Death from Any Cause Up to 31 Months

secondary Outcomes

description
DCR by BICR (with Pembrolizumab) is defined as the number of participants who achieve a BOR of complete response (CR), partial response (PR), or stable disease (SD) lasting 16 or more weeks divided by the total number of participants randomized to each treatment arm.
measure
Percentage of Participant With Disease Control Rate (DCR) by BICR (With Pembrolizumab)
time Frame
Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
description
DCR by BICR (with or without Pembrolizumab) is defined as the number of participants who achieve a BOR of CR, PR, or SD lasting 16 or more weeks divided by the total number of participants randomized to each treatment arm.
measure
Percentage of Participant With DCR by BICR (With or Without Pembrolizumab)
time Frame
Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
description
PFS2 is defined as the time from randomization to disease progression on the next line of treatment or death from any cause in the absence of observed disease progression.
measure
PFS2 (With Pembrolizumab)
time Frame
Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months
description
PFS2 is defined as the time from randomization to disease progression on the next line of treatment or death from any cause in the absence of observed disease progression.
measure
PFS2 (With or Without Pembrolizumab)
time Frame
Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months
description
ORR is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of participants randomized to each treatment arm.
measure
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR (With Pembrolizumab)
time Frame
Baseline through Disease Progression or Death Up to 31 Months
description
ORR is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of participants randomized to each treatment arm.
measure
ORR: Percentage of Participants With CR or PR by BICR (With or Without Pembrolizumab)
time Frame
Baseline through Disease Progression or Death Up to 31 Months
description
DoR was defined as the time from the date that measurement criteria for CR or PR (whichever is first recorded) were first met until the first date that disease was recurrent or documented disease progression was observed, or the date of death from any cause in the absence of documented disease progression or recurrence. The DOR according to both BICR and investigator-assessed BOR was evaluated per RECIST 1.1 criteria.
measure
Duration of Response (DoR) by BICR (With Pembrolizumab)
time Frame
Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 31 Months
description
DoR was defined as the time from the date that measurement criteria for CR or PR (whichever is first recorded) were first met until the first date that disease was recurrent or documented disease progression was observed, or the date of death from any cause in the absence of documented disease progression or recurrence. The DOR according to both BICR and investigator-assessed BOR was evaluated per RECIST 1.1 criteria.
measure
DOR by BICR (With or Without Pembrolizumab)
time Frame
Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 31 Months
description
Overall survival was defined as the time from randomization until death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data was censored on the last date the participant is known to be alive.
measure
Overall Survival (OS) (With Pembrolizumab)
time Frame
Baseline to Date of Death from Any Cause Up to 38 Months
description
Overall survival was defined as the time from randomization until death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the participant is known to be alive.
measure
OS (With or Without Pembrolizumab)
time Frame
Baseline to Date of Death from Any Cause Up to 38 Months
description
Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with Pembrolizumab)
measure
Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 by BICR (With Pembrolizumab)
time Frame
Baseline through Central Nervous System (CNS) Progression or Death up to 31 Months
description
Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with or without Pembrolizumab)
measure
Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per RECIST 1.1 by BICR (With or Without Pembrolizumab)
time Frame
Baseline through CNS Progression or Death Up to 31 Months

Full study description

brief Summary: The reason for this study is to see if the study drug selpercatinib compared to a standard treatment is effective and safe in participants with rearranged during transfection (RET) fusion-positive non-squamous non-small cell lung cancer (NSCLC) that has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.

Source references

references

citation
Duke ES, Bradford D, Sinha AK, Li X, Mishra-Kalyani PS, de Claro RA, Larkins E, Drezner N. Selpercatinib and the Crossover Conundrum: Potential Impact of Postprogression Therapies on Overall Survival. J Clin Oncol. 2026 May 20;44(15):1457-1464. doi: 10.1200/JCO-25-02375. Epub 2026 Apr 17.
pmid
41996652
type
DERIVED
citation
Perol M, Solomon BJ, Goto K, Park K, Nadal E, Bria E, Martin C, Bar J, Williams JN, Puri T, Li J, Uh MK, Lin BK, Zhou C. CNS Protective Effect of Selpercatinib in First-Line RET Fusion-Positive Advanced Non-Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 20;42(21):2500-2505. doi: 10.1200/JCO.24.00724. Epub 2024 Jun 3.
pmid
38828957
type
DERIVED
citation
Zhou C, Solomon B, Loong HH, Park K, Perol M, Arriola E, Novello S, Han B, Zhou J, Ardizzoni A, Mak MP, Santini FC, Elamin YY, Drilon A, Wolf J, Payakachat N, Uh MK, Rajakumar D, Han H, Puri T, Soldatenkova V, Lin AB, Lin BK, Goto K; LIBRETTO-431 Trial Investigators. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. N Engl J Med. 2023 Nov 16;389(20):1839-1850. doi: 10.1056/NEJMoa2309457. Epub 2023 Oct 21.
pmid
37870973
type
DERIVED
citation
Claerhout S, Lehnert S, Vander Borght S, Spans L, Dooms C, Wauters E, Vansteenkiste J, Weynand B, Deraedt K, Bourgain C, Vanden Bempt I. Targeted RNA sequencing for upfront analysis of actionable driver alterations in non-small cell lung cancer. Lung Cancer. 2022 Apr;166:242-249. doi: 10.1016/j.lungcan.2022.02.013. Epub 2022 Mar 1.
pmid
35378489
type
DERIVED
citation
Solomon BJ, Zhou CC, Drilon A, Park K, Wolf J, Elamin Y, Davis HM, Soldatenkova V, Sashegyi A, Lin AB, Lin BK, F Loong HH, Novello S, Arriola E, Perol M, Goto K, Santini FC. Phase III study of selpercatinib versus chemotherapy +/- pembrolizumab in untreated RET positive non-small-cell lung cancer. Future Oncol. 2021 Mar;17(7):763-773. doi: 10.2217/fon-2020-0935. Epub 2020 Nov 5.
pmid
33150799
type
DERIVED